All Three Supersystems—Nervous, Vascular, and Immune—Contribute to the Cortical Infarcts After Subarachnoid Hemorrhage

所有三个超系统-神经，血管和免疫-都有助于蛛网膜下腔出血后的皮质梗塞

The recently published DISCHARGE-1 trial supports the observations of earlier autopsy and neuroimaging studies that almost 70% of all focal brain damage after aneurysmal subarachnoid hemorrhage are anemic infarcts of the cortex, often also affecting the white matter immediately below. The infarcts are not limited by the usual vascular territories. About two-fifths of the ischemic damage occurs within ~ 48 h; the remaining three-fifths are delayed (within ~ 3 weeks). Using neuromonitoring technology in combination with longitudinal neuroimaging, the entire sequence of both early and delayed cortical infarct development after subarachnoid hemorrhage has recently been recorded in patients. Characteristically, cortical infarcts are caused by acute severe vasospastic events, so-called spreading ischemia, triggered by spontaneously occurring spreading depolarization. In locations where a spreading depolarization passes through, cerebral blood flow can drastically drop within a few seconds and remain suppressed for minutes or even hours, often followed by high-amplitude, sustained hyperemia. In spreading depolarization, neurons lead the event, and the other cells of the neurovascular unit (endothelium, vascular smooth muscle, pericytes, astrocytes, microglia, oligodendrocytes) follow. However, dysregulation in cells of all three supersystems-nervous, vascular, and immune-is very likely involved in the dysfunction of the neurovascular unit underlying spreading ischemia. It is assumed that subarachnoid blood, which lies directly on the cortex and enters the parenchyma via glymphatic channels, triggers these dysregulations. This review discusses the neuroglial, neurovascular, and neuroimmunological dysregulations in the context of spreading depolarization and spreading ischemia as critical elements in the pathogenesis of cortical infarcts after subarachnoid hemorrhage.

最近发表的DISCHARGE-1试验支持早期尸检和神经影像学研究的观察结果，即动脉瘤性蛛网膜下腔出血后几乎70% 的局灶性脑损伤是皮质的贫血性梗塞，通常也会影响正下方的白质。梗塞不受通常的血管区域的限制。约5分之2的缺血性损伤发生在 ~ 48小时内; 其余5分之3延迟 (~ 3周内)。使用神经监测技术结合纵向神经影像学，最近已在患者中记录了蛛网膜下腔出血后早期和延迟的皮质梗塞发展的整个序列。典型地，皮层梗塞是由急性严重血管痉挛事件引起的，所谓的扩散性缺血，由自发发生的扩散性去极化触发。在扩散去极化通过的位置，脑血流量可以在几秒钟内急剧下降，并保持抑制数分钟甚至数小时，通常随后是高振幅，持续充血。在扩散去极化中，神经元引导事件，并且随后是神经血管单元的其他细胞 (内皮、血管平滑肌、周细胞、星形胶质细胞、小胶质细胞、少突胶质细胞)。然而，所有三个超系统 (神经，血管和免疫) 的细胞中的失调很可能与扩散性缺血潜在的神经血管单元的功能障碍有关。假定蛛网膜下血液直接位于皮质上并通过淋巴通道进入实质，会触发这些失调。这篇综述讨论了在扩散去极化和扩散缺血的背景下神经胶质，神经血管和神经免疫学失调，这是蛛网膜下腔出血后皮质梗塞发病机理的关键因素。

REF: Dreier JP, Joerk A, Uchikawa H, et al. All Three Supersystems-Nervous, Vascular, and Immune-Contribute to the Cortical Infarcts After Subarachnoid Hemorrhage. Transl Stroke Res. Published online April 30, 2024. doi:10.1007/s12975-024-01242-z PMID: 38689162

Integrating Bulk RNA and Single-Cell Sequencing Data Unveils Efferocytosis Patterns and ceRNA Network in Ischemic Stroke

整合大量RNA和单细胞测序数据揭示缺血性卒中的胞吞模式和ceRNA网络

Excessive inflammatory response following ischemic stroke (IS) injury is a key factor affecting the functional recovery of patients. The efferocytic clearance of apoptotic cells within ischemic brain tissue is a critical mechanism for mitigating inflammation, presenting a promising avenue for the treatment of ischemic stroke. However, the cellular and molecular mechanisms underlying efferocytosis in the brain after IS and its impact on brain injury and recovery are poorly understood. This study explored the roles of inflammation and efferocytosis in IS with bioinformatics. Three Gene Expression Omnibus Series (GSE) (GSE137482-3 m, GSE137482-18 m, and GSE30655) were obtained from NCBI (National Center for Biotechnology Information) and GEO (Gene Expression Omnibus). Differentially expressed genes (DEGs) were processed for GSEA (Gene Set Enrichment Analysis), GO (Gene Ontology Functional Enrichment Analysis), and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analyses. Efferocytosis-related genes were identified from the existing literature, following which the relationship between Differentially Expressed Genes (DEGs) and efferocytosis-related genes was examined. The single-cell dataset GSE174574 was employed to investigate the distinct expression profiles of efferocytosis-related genes. The identified hub genes were verified using the dataset of human brain and peripheral blood sample datasets GSE56267 and GSE122709. The dataset GSE215212 was used to predict competing endogenous RNA (ceRNA) network, and GSE231431 was applied to verify the expression of differential miRNAs. At last, the middle cerebral artery (MCAO) model was established to validate the efferocytosis process and the expression of hub genes. DEGs in two datasets were significantly enriched in pathways involved in inflammatory response and immunoregulation. Based on the least absolute shrinkage and selection operator (LASSO) analyses, we identified hub efferocytosis-related genes (Abca1, C1qc, Ptx3, Irf5, and Pros1) and key transcription factors (Stat5). The scRNA-seq analysis showed that these hub genes were mainly expressed in microglia and macrophages which are the main cells with efferocytosis function in the brain. We then identified miR-125b-5p as a therapeutic target of IS based on the ceRNA network. Finally, we validated the phagocytosis and clearance of dead cells by efferocytosis and the expression of hub gene Abca1 in MCAO mice models.

缺血性卒中 (IS) 损伤后过度炎症反应是影响患者功能恢复的关键因素。缺血性脑组织中凋亡细胞的有效清除是减轻炎症的关键机制，为缺血性中风的治疗提供了一条有希望的途径。然而，人们对IS后大脑中渗出的细胞和分子机制及其对脑损伤和恢复的影响知之甚少。本研究利用生物信息学方法探讨了炎症和胞浆作用在IS中的作用。从NCBI (国家生物技术信息中心) 和GEO (基因表达综合) 获得了三个基因表达综合系列 (GSE) (GSE137482-3 m，GSE137482-18 m和GSE30655)。对差异表达基因 (DEGs) 进行处理，以进行GSEA (基因集富集分析)，GO (基因本体功能富集分析) 和KEGG (京都基因和基因组百科全书) 途径分析。从现有文献中鉴定出与胞吞相关的基因，然后检查差异表达基因 (DEGs) 与胞吞相关基因之间的关系。单细胞数据集GSE174574用于研究胞吐相关基因的独特表达谱。使用人脑和外周血样品数据集GSE56267和gse122709的数据集验证鉴定的枢纽基因。数据集GSE215212用于预测竞争性内源性RNA (ceRNA) 网络，GSE231431用于验证差异mirna的表达。最后，建立大脑中动脉 (MCAO) 模型，以验证hub基因的分泌过程和表达。两个数据集中的DEGs在参与炎症反应和免疫调节的途径中显著富集。基于最小绝对收缩和选择算子 (LASSO) 分析，我们确定了与hub分泌相关的基因 (Abca1，C1qc，Ptx3，Irf5和Pros1) 和关键转录因子 (Stat5)。Scrna-seq分析表明，这些hub基因主要在小胶质细胞和巨噬细胞中表达，而小胶质细胞和巨噬细胞是大脑中具有分泌功能的主要细胞。然后，我们基于ceRNA网络将miR-125b-5p确定为IS的治疗靶标。最后，我们在MCAO小鼠模型中验证了死亡细胞的吞噬作用和清除作用以及hub基因Abca1的表达。

REF: Yuan J, Liao YS, Zhang TC, et al. Integrating Bulk RNA and Single-Cell Sequencing Data Unveils Efferocytosis Patterns and ceRNA Network in Ischemic Stroke. Transl Stroke Res. Published online April 28, 2024. doi:10.1007/s12975-024-01255-8 PMID: 38678526

Omega-3 Fatty Acids and Risk of Ischemic Stroke in REGARDS

Omega-3脂肪酸与缺血性中风的风险

We examined associations between lipidomic profiles and incident ischemic stroke in the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. Plasma lipids (n = 195) were measured from baseline blood samples, and lipids were consolidated into underlying factors using exploratory factor analysis. Cox proportional hazards models were used to test associations between lipid factors and incident stroke, linear regressions to determine associations between dietary intake and lipid factors, and the inverse odds ratio weighting (IORW) approach to test mediation. The study followed participants over a median (IQR) of 7 (3.4-11) years, and the case-cohort substudy included 1075 incident ischemic stroke and 968 non-stroke participants. One lipid factor, enriched for docosahexaenoic acid (DHA, an omega-3 fatty acid), was inversely associated with stroke risk in a base model (HR = 0.84; 95%CI 0.79-0.90; P = 8.33 × 10-8) and fully adjusted model (HR = 0.88; 95%CI 0.83-0.94; P = 2.79 × 10-4). This factor was associated with a healthy diet pattern (β = 0.21; 95%CI 0.12-0.30; P = 2.06 × 10-6), specifically with fish intake (β = 1.96; 95%CI 0.95-2.96; P = 1.36 × 10-4). DHA was a mediator between fish intake and incident ischemic stroke (30% P = 5.78 × 10-3). Taken together, DHA-containing plasma lipids were inversely associated with incident ischemic stroke and mediated the relationship between fish intake and stroke risk.

我们研究了卒中 (REGARDS) 队列中地理和种族差异的原因，脂质组学特征与缺血性卒中之间的关联。从基线血液样本中测量血浆脂质 (n = 195)，并使用探索性因素分析将脂质合并为潜在因素。Cox比例风险模型用于测试脂质因素与卒中事件之间的关联，线性回归用于确定饮食摄入与脂质因素之间的关联，以及逆比值比加权 (IORW) 方法用于测试中介作用。该研究对参与者进行了中位数 (IQR) 7 (3.4-11) 年的随访，病例队列子研究包括1075例缺血性卒中和968例非卒中参与者。一种富含二十二碳六烯酸 (DHA，一种omega-3脂肪酸) 的脂质因子在基础模型 (HR = 0.84; 95% CI 0.79-0.90; P = 8.33 × 10-8) 和完全调整模型 (HR = 0.88；95% 置信区间0.83-0.94; P = 2.79 × 10-4)。该因素与健康的饮食模式有关 (β = 0.21; 95% CI 0.12-0.30; P = 2.06 × 10-6)，特别是与鱼的摄入量有关 (β = 1.96; 95% CI 0.95-2.96; P = 1.36 × 10-4)。DHA是鱼类摄入量与缺血性中风之间的中介因素 (30% P = 5.78 × 10-3)。总之，含DHA的血浆脂质与缺血性中风的发生呈负相关，并介导了鱼类摄入量与中风风险之间的关系。

REF: Ament Z, Patki A, Bhave VM, et al. Omega-3 Fatty Acids and Risk of Ischemic Stroke in REGARDS. Transl Stroke Res. Published online April 27, 2024. doi:10.1007/s12975-024-01256-7 PMID: 38676880

Haptoglobin Attenuates Cerebrospinal Fluid Hemoglobin-Induced Neurological Deterioration in Sheep

触珠蛋白减轻绵羊脑脊液血红蛋白引起的神经系统恶化

Secondary brain injury (SBI) occurs with a lag of several days post-bleeding in patients with aneurysmal subarachnoid hemorrhage (aSAH) and is a strong contributor to mortality and long-term morbidity. aSAH-SBI coincides with cell-free hemoglobin (Hb) release into the cerebrospinal fluid. This temporal association and convincing pathophysiological concepts suggest that CSF-Hb could be a targetable trigger of SBI. However, sparse experimental evidence for Hb's neurotoxicity in vivo defines a significant research gap for clinical translation. We modeled the CSF-Hb exposure observed in aSAH patients in conscious sheep, which allowed us to assess neurological functions in a gyrencephalic species. Twelve animals were randomly assigned for 3-day bi-daily intracerebroventricular (ICV) injections of either Hb or Hb combined with the high-affinity Hb scavenger protein haptoglobin (Hb-Hp, CSL888). Repeated CSF sampling confirmed clinically relevant CSF-Hb concentrations. This prolonged CSF-Hb exposure over 3 days resulted in disturbed movement activity, reduced food intake, and impaired observational neuroscores. The Hb-induced neurotoxic effects were significantly attenuated when Hb was administered with equimolar haptoglobin. Preterminal magnetic resonance imaging (MRI) showed no CSF-Hb-specific structural brain alterations. In both groups, histology demonstrated an inflammatory response and revealed enhanced perivascular histiocytic infiltrates in the Hb-Hp group, indicative of adaptive mechanisms. Heme exposure in CSF and iron deposition in the brain were comparable, suggesting comparable clearance efficiency of Hb and Hb-haptoglobin complexes from the intracranial compartment. We identified a neurological phenotype of CSF-Hb toxicity in conscious sheep, which is rather due to neurovascular dysfunction than structural brain injury. Haptoglobin was effective at attenuating CSF-Hb-induced neurological deterioration, supporting its therapeutic potential.

继发性脑损伤 (SBI) 在动脉瘤性蛛网膜下腔出血 (aSAH) 患者出血后延迟数天发生，并且是死亡率和长期发病率的重要因素。Asah-sbi与无细胞血红蛋白 (Hb) 释放到脑脊液中一致。这种时间关联和令人信服的病理生理学概念表明，csf-hb可能是SBI的可靶向触发因素。然而，Hb体内神经毒性的稀疏实验证据定义了临床翻译的重大研究空白。我们对清醒绵羊aSAH患者中观察到的csf-hb暴露进行了建模，这使我们能够评估脑回物种的神经功能。随机分配十二只动物进行3天，每天两次的脑室内 (ICV) 注射Hb或Hb与高亲和力Hb清除剂蛋白触珠蛋白 (hb-hp，CSL888) 的组合。重复的CSF采样证实了临床相关的csf-hb浓度。长时间的csf-hb暴露超过3天，导致运动活动受到干扰，食物摄入量减少和观察性神经核受损。当Hb与等摩尔触珠蛋白一起使用时，Hb诱导的神经毒性作用显着减弱。终末磁共振成像 (MRI) 未显示csf-hb特异性脑结构改变。在两组中，组织学均显示炎症反应，并显示hb-hp组血管周围组织细胞浸润增强，表明存在适应性机制。脑脊液中血红素的暴露和大脑中铁的沉积是相当的，这表明颅内隔室中Hb和Hb-触珠蛋白复合物的清除效率相当。我们在有意识的绵羊中确定了csf-hb毒性的神经系统表型，这与神经血管功能障碍而不是结构性脑损伤有关。触珠蛋白可有效减轻csf-hb诱导的神经系统恶化，支持其治疗潜力。

REF: Thomson BR, Schwendinger N, Beckmann K, et al. Haptoglobin Attenuates Cerebrospinal Fluid Hemoglobin-Induced Neurological Deterioration in Sheep. Transl Stroke Res. Published online April 23, 2024. doi:10.1007/s12975-024-01254-9 PMID: 38652234

Blood DNA Methylation Analysis Reveals a Distinctive Epigenetic Signature of Vasospasm in Aneurysmal Subarachnoid Hemorrhage

血液DNA甲基化分析揭示了动脉瘤性蛛网膜下腔出血中血管痉挛的独特表观遗传特征

Vasospasm is a potentially preventable cause of poor prognosis in patients with aneurysmal subarachnoid hemorrhage (aSAH). Epigenetics might provide insight on its molecular mechanisms. We aimed to analyze the association between differential DNA methylation (DNAm) and development of vasospasm. We conducted an epigenome-wide association study in 282 patients with aSAH admitted to our hospital. DNAm was assessed with the EPIC Illumina chip (> 850 K CpG sites) in whole-blood samples collected at hospital admission. We identified differentially methylated positions (DMPs) at the CpG level using Cox regression models adjusted for potential confounders, and then we used the DMP results to find differentially methylated regions (DMRs) and enriched biological pathways. A total of 145 patients (51%) experienced vasospasm. In the DMP analysis, we identified 31 CpGs associated with vasospasm at p-value < 10-5. One of them (cg26189827) was significant at the genome-wide level (p-value < 10-8), being hypermethylated in patients with vasospasm and annotated to SUGCT gene, mainly expressed in arteries. Region analysis revealed 13 DMRs, some of them annotated to interesting genes such as POU5F1, HLA-DPA1, RUFY1, and CYP1A1. Functional enrichment analysis showed the involvement of biological processes related to immunity, inflammatory response, oxidative stress, endothelial nitric oxide, and apoptosis. Our findings show, for the first time, a distinctive epigenetic signature of vasospasm in aSAH, establishing novel links with essential biological pathways, including inflammation, immune responses, and oxidative stress. Although further validation is required, our results provide a foundation for future research into the complex pathophysiology of vasospasm.

血管痉挛是动脉瘤性蛛网膜下腔出血 (aSAH) 患者预后不良的潜在可预防原因。表观遗传学可能提供对其分子机制的见解。我们旨在分析差异DNA甲基化 (DNAm) 与血管痉挛发展之间的关系。我们对我院收治的282例aSAH患者进行了一项表观基因组全关联研究。用EPIC Illumina芯片 (> 850 K CpG位点) 在入院时收集的全血样本中评估DNAm。我们使用针对潜在混杂因素调整的Cox回归模型在CpG水平鉴定差异甲基化位置 (DMP)，然后我们使用DMP结果来寻找差异甲基化区域 (dmr) 和富集的生物学途径。共有145名患者 (51%) 经历了血管痉挛。在DMP分析中，我们确定了31个与p值 <10-5的血管痉挛相关的cpg。其中之一 (cg26189827) 在全基因组水平上具有显着性 (p值 <10-8)，在血管痉挛患者中被高甲基化，并注释为SUGCT基因，主要在动脉中表达。区域分析揭示了13个dmr，其中一些注释了有趣的基因，例如POU5F1，HLA-DPA1，RUFY1和CYP1A1。功能富集分析显示涉及与免疫，炎症反应，氧化应激，内皮一氧化氮和细胞凋亡有关的生物学过程。我们的研究结果首次显示了aSAH中血管痉挛的独特表观遗传特征，与基本生物学途径建立了新的联系，包括炎症，免疫反应和氧化应激。尽管需要进一步验证，但我们的结果为将来研究血管痉挛的复杂病理生理学奠定了基础。

REF: Fernández-Pérez I, Jiménez-Balado J, Macias-Gómez A, et al. Blood DNA Methylation Analysis Reveals a Distinctive Epigenetic Signature of Vasospasm in Aneurysmal Subarachnoid Hemorrhage. Transl Stroke Res. Published online April 23, 2024. doi:10.1007/s12975-024-01252-x PMID: 38649590

Glymphatic Impairment Associated with Neurocognitive Dysfunction in Moyamoya Disease

烟雾病中与神经认知功能障碍相关的淋巴功能障碍

Glymphatic system alterations have been proved to be associated with cognitive dysfunction in neurodegenerative diseases. The glymphatic pathway has not been elucidated in moyamoya disease (MMD), which was recognized as a chronic hypoperfusion model for neurodegenerative disease. Here, we aimed to investigate the glymphatic system activity and its relation with neurocognition, and associated hallmarks in MMD. We prospectively recruited 30 MMD patients and 30 matched healthy controls (HC). Participants underwent MRI and neurocognition evaluation. The glymphatic function was assessed by diffusion tensor image analysis along perivascular space (DTI-ALPS) index. Gray matter volume (GMV) and microstructural alterations were calculated. Neurodegenerative-related serum biomarkers were examined. The mediation effect of ALPS index in the associations between variables and neurocognition were further explored. A lower ALPS index was identified in patients with MMD (P < 0.001). The decreased ALPS index was significantly correlated with declined neurocognitive performance. Moreover, the reduced ALPS index was notably linked with lower total GMV% and deep GMV% (P < 0.01). Microstructural changes in the periventricular areas were detected and associated with ALPS index in MMD. Serum neurodegenerative biomarkers (ApoE, Aβ40, Aβ42, and Aβ42/Aβ40) were significantly elevated and related to ALPS index. Additionally, the ALPS index significantly mediated the associations of microstructural alterations and ApoE level with neurocognitive dysfunction. The ALPS index was notably lower MMD in patients, suggesting the utility as a marker of potential glymphatic dysfunction. The index acted as a significant mediator in neurocognitive dysfunction. These findings indicated that glymphatic impairment may interact with MMD-related pathophysiological processes.

淋巴系统改变已被证明与神经退行性疾病的认知功能障碍有关。在烟雾病 (MMD) 中尚未阐明淋巴途径，该病被认为是神经退行性疾病的慢性低灌注模型。在这里，我们旨在研究淋巴系统活动及其与神经认知的关系，以及MMD的相关标志。我们前瞻性地招募了30名MMD患者和30名匹配的健康对照 (HC)。参与者接受MRI和神经认知评估。通过沿血管周围空间的扩散张量图像分析 (dti-alps) 指数评估淋巴功能。计算灰质体积 (GMV) 和微结构改变。检查神经变性相关的血清生物标志物。进一步探讨ALPS指数在变量与神经认知关联中的中介作用。MMD患者的ALPS指数较低 (P <0.001)。ALPS指数下降与神经认知能力下降显著相关。此外，降低的ALPS指数与较低的总GMV % 和深GMV % 显着相关 (P <0.01)。检测到脑室周围区域的微观结构变化，并与MMD中的ALPS指数相关。血清神经变性生物标志物 (ApoE，Aβ40，Aβ42和Aβ42/Aβ40) 显着升高，并与ALPS指数相关。此外，ALPS指数显着介导了微结构改变和ApoE水平与神经认知功能障碍的关联。患者的ALPS指数明显较低，表明该效用可作为潜在的淋巴功能障碍的标志物。该指数在神经认知功能障碍中起着重要的中介作用。这些发现表明，淋巴功能障碍可能与MMD相关的病理生理过程相互作用。

REF: Zeng C, Zhai Y, Ge P, et al. Glymphatic Impairment Associated with Neurocognitive Dysfunction in Moyamoya Disease. Transl Stroke Res. Published online April 17, 2024. doi:10.1007/s12975-024-01250-z PMID: 38630409

Depth-Specific Hypoxic Responses to Spreading Depolarizations in Gyrencephalic Swine Cortex Unveiled by Photoacoustic Imaging

光声成像揭示了脑回猪皮层中扩散去极化的深度特异性低氧反应

Spreading depolarizations (SDs) are a marker of brain injury and have a causative effect on ischemic lesion progression. The hemodynamic responses elicited by SDs are contingent upon the metabolic integrity of the affected tissue, with vasoconstrictive reactions leading to pronounced hypoxia often indicating poor outcomes. The stratification of hemodynamic responses within different cortical layers remains poorly characterized. This pilot study sought to elucidate the depth-specific hemodynamic changes in response to SDs within the gray matter of the gyrencephalic swine brain. Employing a potassium chloride-induced SD model, we utilized multispectral photoacoustic imaging (PAI) to estimate regional cerebral oxygen saturation (rcSO2%) changes consequent to potassium chloride-induced SDs. Regions of interest were demarcated at three cortical depths covering up to 4 mm. Electrocorticography (ECoG) strips were placed to validate the presence of SDs. Through PAI, we detected 12 distinct rcSO2% responses, which corresponded with SDs detected in ECoG. Notably, a higher frequency of hypoxic responses was observed in the deeper cortical layers compared to superficial layers, where hyperoxic and mixed responses predominated (p < 0.001). This data provides novel insights into the differential oxygenation patterns across cortical layers in response to SDs, underlining the complexity of cerebral hemodynamics post-injury.

扩散去极化 (SDs) 是脑损伤的标志，对缺血性病变的进展具有致病作用。SDs引起的血液动力学反应取决于受影响组织的代谢完整性，血管收缩反应导致明显的缺氧通常表明不良结果。不同皮质层内的血液动力学反应的分层仍然难以表征。这项初步研究旨在阐明脑回猪脑灰质内SDs响应的深度特异性血液动力学变化。采用氯化钾诱导的SD模型，我们利用多光谱光声成像 (PAI) 来估算氯化钾诱导的SD引起的局部脑氧饱和度 (rcSO2 %) 变化。在覆盖多达4毫米的三个皮质深度处划分感兴趣区域。放置皮质电描记术 (ECoG) 条以验证SDs的存在。通过PAI，我们检测到12种不同的rcSO2% 响应，这与ECoG中检测到的SDs相对应。值得注意的是，与浅表层相比，在更深的皮质层中观察到更高频率的低氧反应，其中高氧和混合反应占主导地位 (p <0.001)。这些数据为响应SDs的跨皮质层的差异氧合模式提供了新颖的见解，强调了损伤后脑血流动力学的复杂性。

REF: Santos E, Lopez-Navarro JM, Suarez-Gutierrez MA, et al. Depth-Specific Hypoxic Responses to Spreading Depolarizations in Gyrencephalic Swine Cortex Unveiled by Photoacoustic Imaging. Transl Stroke Res. Published online April 16, 2024. doi:10.1007/s12975-024-01247-8 PMID: 38622426

Flow-Diverting Devices in the Treatment of Vertebral Artery Aneurysms: Insights into Efficacy and Safety from a Systematic Review and Meta-analysis

引流装置治疗椎动脉动脉瘤: 从系统评价和荟萃分析洞察疗效和安全性

The objective of this study is to conduct a systematic review and meta-analysis aimed at evaluating the efficacy and safety of flow-diverting devices (FDs) treatment for intracranial vertebral artery (VA) aneurysms. We searched PubMed, Web of Science, OVID, and Embase for English-language studies up to February 2024 and included clinical studies on FD treatment of intracranial VA aneurysms. Sensitivity analysis evaluated outcome stability. Of 2273 articles, 29 studies involving 541 aneurysms treated with FDs were included. Based on the Methodological Index for Non-Randomized Studies (MINORS), six were high-quality and 23 moderate quality. FD treatment showed a 95% rate of favorable clinical outcomes (95% CI, 89-99%), 81% (95% CI, 74-88%) complete aneurysmal occlusion, 4% (95% CI, 2-7%) ischemic complication incidence, 1% (95% CI, 0-3%) hemorrhagic complication incidence, 95% (95% CI, 87-100%) posterior inferior cerebellar artery (PICA) preservation, and 6% (95% CI, 3-10%) in-stent stenosis or occlusion across clinical and angiographic follow-up periods of 13.62 months (95% CI, 10.72-16.52) and 11.85 months (95% CI, 9.36-14.33), respectively. Subgroup analyses, based on a 12-month angiographic follow-up threshold, indicated no statistically significant differences in rates of complete aneurysm occlusion, PICA preservation, or in-stent stenosis or occlusion incidence (p > 0.05) between subgroups. Moreover, significant differences were observed in clinical and angiographic outcomes between ruptured and unruptured aneurysms, particularly in hemorrhagic complications (p < 0.05), without significant disparity in ischemic complications (p > 0.05). The results' stability was confirmed via sensitivity analysis. FDs treatment for VA aneurysms is efficacious and safe, offering high rates of positive clinical and angiographic outcomes with minimal complications, underscoring FDs' viability as a treatment option for VA aneurysms. The study was registered with PROSPERO (registration number: CRD42024499894).

这项研究的目的是进行系统回顾和荟萃分析，旨在评估引流装置 (FDs) 治疗颅内椎动脉 (VA) 动脉瘤的有效性和安全性。我们在PubMed、Web of Science、OVID和Embase中搜索了截至2024年2月的英语研究，并纳入了FD治疗颅内VA动脉瘤的临床研究。敏感性分析评估结果稳定性。在2273篇文章中，纳入了29项研究，涉及FDs治疗的541个动脉瘤。根据非随机研究 (未成年人) 的方法学指标，6项为高质量，23项为中等质量。FD治疗显示出95% 的有利临床结果 (95% CI，89-99%)，81% (95% CI，74-88%) 完全动脉瘤闭塞，4% (95% CI，2-7%) 缺血性并发症发生率，1% (95% CI，0-3%) 出血性并发症发生率，95% (95% CI，87-100%)在临床和血管造影随访期间分别为13.62个月 (95% CI，10.72-16.52) 和11.85个月 (95% CI，9.36-6%)，保留小脑后下动脉 (PICA) 和14.33 (95% CI，3-10%) 支架内狭窄或闭塞。基于12个月血管造影随访阈值的亚组分析表明，亚组之间完全动脉瘤闭塞、PICA保留或支架内狭窄或闭塞发生率无统计学显著差异 (p> 0.05)。此外，在破裂和未破裂动脉瘤之间的临床和血管造影结果中观察到显着差异，特别是在出血性并发症中 (p <0.05)，而在缺血性并发症中没有显着差异 (p> 0.05)。敏感性分析证实了结果的稳定性。FDs治疗VA动脉瘤是有效和安全的，提供高比率的积极的临床和血管造影结果与最小的并发症，强调FDs作为VA动脉瘤的治疗选择的可行性。该研究在PROSPERO注册 (注册号: CRD42024499894)。

REF: Liu C, Wu X, Guo K, et al. Flow-Diverting Devices in the Treatment of Vertebral Artery Aneurysms: Insights into Efficacy and Safety from a Systematic Review and Meta-analysis. Transl Stroke Res. Published online April 11, 2024. doi:10.1007/s12975-024-01251-y PMID: 38602659

Three Pillars of Recovery After Aneurysmal Subarachnoid Hemorrhage: A Narrative Review

动脉瘤性蛛网膜下腔出血后恢复的三大支柱: 叙述性回顾

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating neurologic disease with high mortality and disability. There have been global improvements in survival, which has contributed to the prevalence of patients living with long-term sequelae related to this disease. The focus of active research has traditionally centered on acute treatment to reduce mortality, but now there is a great need to study the course of short- and long-term recovery in these patients. In this narrative review, we aim to describe the core pillars in the preservation of cerebral function, prevention of complications, the recent literature studying neuroplasticity, and future directions for research to enhance recovery outcomes following aSAH.

动脉瘤性蛛网膜下腔出血 (aSAH) 是一种具有高死亡率和致残率的神经系统疾病。全球生存率有所提高，这导致患有与该疾病相关的长期后遗症的患者的患病率。传统上，积极研究的重点一直集中在急性治疗以降低死亡率，但是现在非常需要研究这些患者的短期和长期康复过程。在这篇叙述性综述中，我们旨在描述脑功能保护的核心支柱，并发症的预防，最近研究神经可塑性的文献，以及未来的研究方向，以提高aSAH后的恢复结果。

REF: Ryan D, Ikramuddin S, Alexander S, Buckley C, Feng W. Three Pillars of Recovery After Aneurysmal Subarachnoid Hemorrhage: A Narrative Review. Transl Stroke Res. Published online April 11, 2024. doi:10.1007/s12975-024-01249-6 PMID: 38602660